BIOLOGY OF HHV8/KSHV G PROTEIN COUPLED RECEPTOR

描述：该项目的重点是HHV-8的G蛋白偶联受体 它被发现与卡波西肉瘤有关。最近是这样的 已证明该受体通过磷脂酰肌醇发挥作用 1，4，5-三磷酸-钙-蛋白激酶C信号转导通路 诱导细胞增殖和转化；提示HHV-8/GPCR可能 在异常扩散中发挥必要的作用，如果不是充分的话 表现为KS细胞或淋巴瘤B细胞。这样做的目的是 研究目的是了解HHV-8GPCR的生物学及其在人类免疫缺陷病毒感染中的作用 KS的发病机制。提出了三个具体目标。第一个是 描述了潜在调控的信号机制和模式 HHV-8GPCR的表达及其生物学效应 多种细胞类型，如Cos、293T、NIH3T3、上皮细胞和B细胞。这个 二是发现基于HHV-8GPCR的高亲和力、特异性配体 类似于已知的趋化因子。三是要明确党的作用 HHV-8GPCR在疾病发病机制中的作用

DESCRIPTION: This project focuses on a G protein-coupled receptor of HHV-8 which was found to be associated with Kaposi's sarcoma. It has recently been shown that this receptor functions via the phosphoinositide-inositol 1,4,5-triphosphate-calcium-protein kinase C signal transduction pathway, to induce cell proliferation and transformation; suggesting that HHV-8/GPCR may play a necessary, if not sufficient role in the abnormal proliferation exhibited by KS cells or lymphomatous B cells. The objectives of this research are to understand the biology of HHV-8 GPCR, and its role in the pathogenesis of KS. Three specific aims are proposed. The first is to delineate the signaling mechanisms and modes of potential regulation of HHV-8 GPCR, and the biological consequences of HHV-8 GPCR expression in various cell types, such as cos, 293T, NIH 3T3, epithelial and B cells. The second is to discover high affinity, specific ligands for HHV-8 GPCR based on analogy to known chemokines. The third is to determine the roles of HHV-8 GPCR in disease pathogenesis.